Coexistent Eosinophilic Esophagitis and Dysplastic Barrett's Esophagus With Rapid Eosinophilic Infiltration of Neosquamous Mucosa After Radiofrequency Ablation

ABSTRACT The coexistence of eosinophilic esophagitis (EoE) and Barrett's esophagus (BE) is rare despite the known association of gastroesophageal reflux disease with both conditions. Radiofrequency ablation is an effective endoscopic eradication therapy in patients with dysplastic BE. However, the efficacy and outcomes of radiofrequency ablation in patients with concomitant EoE and BE are not well known. We report a case of rapid eosinophilic infiltration of the neosquamous mucosa after the complete eradication of long-segment dysplastic BE in a patient with coexisting BE and EoE.

He had a good response to RFA with the eradication of 75% of the Barrett's segment after 3 RFA treatments with a focal RFA catheter (Halo 90 Barrx; Medtronic, Minneapolis, MN).Repeat biopsy 8 months after initial RFA, revealed a diffuse eosinophilic infiltration (peak count .50/hpf) of the nondysplastic neosquamous mucosa within the previous dysplastic Barrett's segment and persistence of EoE (peak eosinophil count .25/ hpf) in the proximal esophagus.Despite these new changes of diffuse distal esophageal eosinophilia, he denied any symptoms of dysphagia, heartburn, or chest pain.Medical management was escalated with dupilumab 300 mg weekly because of the persistence of EoE on biopsy.
An additional RFA treatment achieved complete eradication of the long-segment Barrett's, with 4 treatments performed at average follow-up intervals of 4 months.Biopsy from the surveillance endoscopy 4 months after the last RFA revealed diffuse EoE involving the entire length of the neosquamous mucosa with a peak eosinophil count of .50/hpf,along with persistent eosinophilia of the EoE present in the upper esophagus and midesophagus.The patient did not develop any symptoms of dysphagia within 18 months of follow-up, despite the development of EoE in the neosquamous mucosa of the distal esophagus after ablation.

DISCUSSION
BE, in addition to esophageal eosinophilia, is associated with GERD.The coexistence of EoE and dysplastic BE, however, remains rare, with only a few reported cases. 2,5,6We present a rare case of long-segment, dysplastic BE without eosinophilia, responsive to RFA, with the development of EoE within the neosquamous (post-treatment) mucosa within 4 months of RFA treatment.Untreated Barrett's dysplasia is associated with a lifetime esophageal adenocarcinoma risk of up to 5%. 7][10] RFA uses thermal energy derived from electrical current to induce superficial tissue necrosis, which allows for neosquamous epithelium regeneration and minimizes the risks of stricture formation. 11tes of the development of eosinophilia after RFA in patients without EoE have been reported in 2 studies at 2.7% after 1 year in 140 patients and 9% (after RFA or cryotherapy) for dysplastic BE after 3 years with a positive linear correlation between Barrett's esophagus segment length and postablation eosinophilia. 12,13The median postablation eosinophil counts were 15 and 39/hpf (range 5-103). 12,13None of the patients from the above studies had a documented diagnosis of EoE before RFA.Halsey et al found a median eosinophil count of 1/hpf (range 0-14) in the Barrett's segment before ablation, although no pre-RFA esophageal eosinophilia was identified by Villa et al. 12,13 In a retrospective study by Owens et al, patients who had undergone ablation (RFA or photodynamic therapy) for Barrett's dysplasia were followed with endoscopic biopsies of the neosquamous mucosa after ablation.3.4% of the patients (13/385, all following photodynamic therapy) had increased eosinophils ($30/hpf) in the neosquamous mucosa with onset between 83 and 692 days after ablation.There was no dysphagia attributed to eosinophilia or endoscopic signs of EoE.None of the patients had a diagnosis of EoE before ablation. 14This is the first reported case of a patient with known EoE and BE found to have EoE extending into the neosquamous esophagus after RFA and in which the timeframe of eosinophilic infiltration has been documented.Chronic inflammation because of repetitive ablation-induced injury, increased sensitivity of the ablated epithelium to ingested antigens, and ongoing GERD have been proposed as possible etiologies of post-RFA esophageal eosinophilia. 13An increased incidence of proximal esophageal fibrostenotic disease was found on endoscopy in patients with coexistent EoE  and BE (4.7% of 509 patients) along with a male preponderance, in data analyzed from the Swiss Eosinophilic Esophagitis Cohort Study. 15Consistent with the above study, our patient was male and had dysphagia because of esophageal stenoses in the proximal EoE segment, which responded well to dilation, PPI, and dupilumab.No eosinophilia was seen on biopsy of the Barrett's segment; however, eosinophilia within the post-RFA treatment neosquamous mucosa was seen to develop within 4 months after therapy.The development of eosinophilia in the distal esophagus was not associated with new-onset symptoms of esophageal dysfunction.This case demonstrates a good response to RFA in a patient with concomitant EoE and long-segment dysplastic Barrett's and provides interesting insights into the pathophysiology of EoE because high levels of eosinophilia were seen to develop within the neosquamous mucosa within 4 months after RFA ablation, despite the use of high-dose PPI therapy and the absence of significant reflux esophagitis.Further data on the efficacy and outcomes of RFA in patients with coexistent EoE and dysplastic BE is required.In addition, further study of the clinical course and potential significance of post-RFA eosinophilia in patients with and without concomitant EoE may provide additional insights into the pathophysiology of EoE and aid in risk stratification and guide postablation endoscopic surveillance.

DISCLOSURES
Author contributions: P.A. Ameyaw performed the initial chart and literature review to produce the draft manuscript.D. Parsons led concept designing and literature review.A. Mahmoud and R. Marie were responsible for preparing the esophageal microscopy slides and describing the legends.A. Nagar and H.R. Aslanian performed a revision of the final manuscript.

Figure 1 .
Figure 1.Endoscopic image showing circumferential mucosal rings and stenosis in proximal and midesophagus.

Figure 2 .
Figure 2. Endoscopic image showing salmon-colored mucosa of the distal esophagus consistent with Barrett's esophagus.

Figure 3 .
Figure 3. (A) Initial biopsies from the distal esophagus revealed intestinal metaplasia with numerous goblet cells (arrowheads), in addition the columnar cells show enlarged, mildly atypical nuclei both in the gland base and extending to the surface, characteristic of low-grade dysplasia.Magnification: 2003.(B) The proximal esophageal mucosa at 24 cm revealed eosinophil-rich esophagitis with eosinophils numbering .25/high-power field (arrows) and hyperplasia of the basal zone.No lamina propria was present in the biopsies to evaluate subepithelial fibrosis.(C) After radiofrequency ablation, the gastroesophageal junction revealed re-epithelialization by squamous epithelium with eosinophil-rich esophagitis.(D) Concomitant proximal esophageal mucosa (which had not undergone ablation) also continued to show eosinophilic esophagitis.Basal zone hyperplasia, subepithelial fibrosis, and focal eosinophilic microabscesses were noted in several biopsies.